Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)
Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)
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DOI：
10.1073/pnas.231094498
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发表时间：
2001-11-06
影响因子：
11.1
通讯作者：
Baba, A
中科院分区：
文献类型：
--
作者：
Hashimoto, H;Shintani, N;Baba, A
垂体腺苷酸环化酶激活多肽（垂体腺苷酸环化酶激活多肽，PACAP）在进化过程中具有显著的保守性，在哺乳动物大脑中广泛表达。在果蝇中，PACAP同系物的突变会导致行为缺陷，包括嗅觉相关学习功能受损和乙醇敏感性改变。在这里，我们报道了缺乏PACAP基因（PACAP(-/-)）的小鼠的产生。PACAP（-/-）小鼠以预期的孟德尔比例出生，但早期死亡率很高。存活的成年PACAP（-/-）小鼠表现出显著的行为变化；他们在开阔的场地上表现出过度活跃和爆炸性的跳跃行为，在高阶迷宫、涌现和新物体测试中表现出更多的探索行为和更少的焦虑。PACAP（-/-）小鼠脑组织分析结果显示，与野生型小鼠相比，血清素代谢物5-羟吲哚乙酸在皮质和纹状体中略有下降。本研究提供了证据，证明PACAP在精神运动行为的调节中起着以前未被发现的作用。
Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved remarkably during evolution and is widely expressed in the mammalian brain. In Drosophila, mutation of the PACAP homologue results in behavioral defects, including impaired olfaction-associated learning and changes in ethanol sensitivity. Here, we report the generation of mice lacking the PACAP gene (PACAP(-/-)). PACAP(-/-) mice were born in the expected Mendelian ratios but had a high early-mortality rate. The surviving adult PACAP(-/-) mice displayed remarkable behavioral changes; they exhibited hyperactive and explosive jumping behaviors in an open field, increased exploratory behavior, and less anxiety in the elevated plus maze, emergence, and novel-object tests. Analysis of PACAP(-/-) mice brains revealed that the serotonin metabolite 5-hydroxyindoleacetic acid was slightly decreased in the cortex and striatum compared with wild-type mice. The present study provides evidence that PACAP plays a previously uncharacterized role in the regulation of psychomotor behaviors.